Idiotype restriction in human autoantibodies to DNA in systemic lupus erythematosus

Antibodies (Ab) to double stranded DNA (dsDNA) were immunoaffinity-purified from the serum of patient TOF with active systemic lupus erythematosus (SLE). Anti-idiotypic Ab to TOF anti-DNA were raised in rabbit. They were shown to recognize TOF F(ab')2 fragments, but they did not interact with human Ab of other specificities or with TOF IgG depleted of anti-DNA activity. In addition, their binding to TOF idiotype was specifically inhibited by DNA molecules. These anti-idiotype Ab therefore recognized idiotopes associated with a variable region of TOF anti-DNA-combining site. Thirty-one purified IgG anti-DNA preparations from unrelated SLE sera were able to inhibit this idiotype-anti-idiotype reaction by up to 90%. However, there was no linear correlation between anti-dsDNA Ab levels and idiotype-blocking capacity. These findings suggest that, in SLE, the idiotypic repertoire of autoAb to dsDNA is more restricted than thought previously.